17:20 Paracrine Delivery: Therapeutic Biomolecules Produced in Situ
Andreas G. Plückthun, PhD, Professor and Director, Department of Biochemistry, University of Zürich
Cancer will have to be fought with cocktails of therapeutics acting locally, which may have to include therapeutic antibodies against receptors, checkpoint inhibitors, as well as cytokines to modify the tumor microenvironment. We have recently developed
a technology of using non-replicative adenovirus carrying no viral genes, engineered to target desired cells and also to be shielded from the immune response, as a vehicle for simultaneous delivery of multiple genes of therapeutic proteins, produced
and secreted by the infected cells.
Single Cell Selections of Recombinant Antibodies Binding to Circulating Tumor Cells
Peter Kristensen, PhD, Associate Professor, Department of Chemistry and Bioscience, Aalborg University
Metastatic cancer is closely linked to circulating tumor cells. The mechanisms behind the dissemination of cancer through these metastatic seeds however remain incompletely understood. To reveal novel biomarkers, and gain a better understanding of
the underlying mechanisms of cancer metastasis, we have used an advanced single cell selection on circulating tumor cells from patients diagnosed with metastatic colorectal cancer. In the presentation, the potential of single cell selection of
recombinant antibodies will be discussed.
From Systems Biology to Systems Biologics
Sachdev Sidhu, PhD, Professor, Molecular Genetics, The Donnelly Centre, University of Toronto
We have established a platform to combine large-scale systems biology approaches with the discovery and development of new antibody drugs, and to develop efficient, systems-scale strategies to target intracellular signaling networks at the protein
level with ubiquitin variants and other scaffolds. This efficient pipeline connects basic research to translational science in a new model for drug development, which we have termed “Systems Biologics”.
Grp 94, an Intracellular Target of Antibody-Based Immunotherapy of Malignant Diseases – Opportunities and Challenges
Soldano Ferrone, MD, PhD, Professor, Surgery, Massachusetts General Hospital, Harvard Medical School
The scFv W9 has been isolated from a phage display human antibody library. This antibody has the unique specificity to recognize an extracellular epitope of the heat shock protein Grp94. The characteristics and functional properties of this antibody
will be described. In addition, the obstacles to the clinical applications of this and the strategies to overcome them will be discussed.
Novel T Cell Engagers for Targeted Recruitment of Effector Cells to Tumors
Yoram Reiter, PhD, Head, Molecular Immunology, Technion-Israel Institute of Technology
We have developed a new class of recombinant chimerical molecule that serve as T cell engagers to re-direct potent immune effector functions to specifically kill tumor cells. These T cell engagers are based on the genetic fusion of antibody fragments,
specific for tumor cell surface antigens to monomeric HLA molecules that carry immunodominant peptides that can recall potent effector T cells. The molecular feature of these molecules/approaches and their in vitro and in vivo activities
will be described.
Strategies & Challenges for the Next Generation of ADCs
Alain Beck, PhD, Senior Director, Analytical Chemistry, NBEs, Centre d’Immunologie Pierre Fabre; Associate Editor, mAbs
The development of ADCs has benefited from general improvements in the design of therapeutic mAbs and from specific improvements in methods for conjugate synthesis. Diversification of linking strategies and warheads has provided new opportunities
to improve drug delivery to tumors while reducing drug exposure to normal tissues. Protein structural characterization tools such as mass spectrometry are allowing better understanding of ADC structures, stability and biotransformations. This
knowledge contributes to the identification of early-developability criteria for all of the ADC components.
Development of Effective Combination Therapies for Immuno-Oncology
Rakesh Dixit, PhD, Vice President, Safety Assessment, MedImmune, Inc.
This presentation will cover: the rationale for combination therapies in immunotherapy; the challenges of selecting the combination drugs that would give synergism; translational and precision medicine approaches in combination immune-oncology, and
safety considerations in development of the combination drugs.
Developability Strategies to Support Fast to FTIH Studies
Mike Molloy, MSc, Director, Analytical and Characterisation, Biopharm Process Research, GlaxoSmithKline
Two key deliverables for a successful path to First time in Human (FTIH) studies are the selection of a quality molecule and a stable cell line. This presentation will give an insight into how a combination of biophysical characterisation and accelerated
stress delivers a much better understanding of product attributes during the discovery phase of drug development. This workflow is used for screening novel lead panel molecules with respect to their developability, ensuring that the right molecule
is progressed to cell line development.
Integrating Analytical Strategies into a Comprehensive Development Strategy
Thomas Spitznagel, PhD, Senior Vice President, Biopharmaceutical Development & Manufacturing, MacroGenics
Appropriately selected and developed analytics are critical to ensure process development and manufacturing are effectively implemented. Phase appropriate strategies and approaches to developing analytical release, characterization, and in-process
methods will be presented that balance speed, risk, and thoroughness. A variety of case studies across different protein platforms will be used to illustrate examples that ensure the overall development strategy is supported by the appropriate
set of analytical tools.
Protein Gelation at Interfaces: Implications for Aggregation and Particle Formation
Theodore W. Randolph, PhD, Kenneth and Genevieve Gillespie Professor, Department of Chemical and Biological Engineering, University of Colorado
Transient Protein (Gene) Expression: From R&D towards Pharmaceutical Manufacturing
Florian M. Wurm, Dr. rer. nat., Professor Emeritus, Swiss Federal Institute of Technology Lausanne (EPFL); Founder, Chairman, ExcellGene SA
Transient protein (gene) expression (TGE) delivers products in days. HEK-293 cell TGE helped to identify a “better than nature” thrombolytic resulting in the approval of (TNKase “Tenecteplase”). Scale-up R&D resulted in
the first 100 Liter–scale production in the late 1990s. Recent progress in transient protein expression, including viral vector production, delivers grams and tens of grams of high-quality protein/virus vector for preclinical research and,
for clinical use soon?
How Problems of Protein Purification Are Being Addressed across Structural Laboratories in Europe: Insights from the European Research Infrastructure Consortium
Ray Owens, PhD, Professor, Molecular Biology and Head, Oxford Protein Production Facility, University of Oxford
Technology developments to streamline the production of proteins for structural biology have been largely driven by the demands of structural proteomics. However, the purification of increasingly complex proteins and protein assemblies has challenged
traditional high-throughput structural proteomic workflows. The response of a number of academic centres in Instruct, a distributed European Research Infrastructure Consortium (www.structuralbiology.eu) will be reviewed and common trends highlighted.
TNFR2 Antagonism: It Doesn’t Get Any Better - A Treg and Oncogene Targeted Therapy
Denise L. Faustman, MD, PhD, Director, Immunobiology, Massachusetts General Hospital; Associate Professor, Medicine, Harvard Medical School
Tumor necrosis factor receptor-2 (TNFR2) is a signaling molecule found on the surface of the most potent regulatory T-cells; signaling through TNFR2 proliferates cell through NF-kB. TNFR2 is also abundantly expressed on the surface of many human
tumors as on oncogene. We propose that blocking TNFR2 selectively targets abundant TNFR2+ tumor-infiltrating Tregs and directly kill TNFR2-expressing tumors. With multi-year efforts we have created TNFR2 antagonistic antibodies with tumor
The ImmTAC Platform: How Far We Have Come and Where We Are Going
Bent K. Jakobsen, PhD, CSO, Immunocore Ltd.
Immune mobilizing monoclonal TCRs against cancer (ImmTAC™) molecules are a novel class of immunotherapy agent comprised of a soluble T cell receptor (TCR) fused to a T-cell redirecting scFv anti-CD3. ImmTAC molecules offer distinct advantages
over antibody- and cell-based formats, including access to a much larger pool of antigens in a soluble platform. The lead ImmTAC molecule, IMCgp100, has demonstrated encouraging preliminary anti-tumour activity in patients with metastatic